Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML

NCT ID: NCT05177731

Last Updated: 2024-10-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2024-12-31

Brief Summary

This research is being done to assess the therapeutic efficacy and safety of a promising (venetoclax and decitabine) versus conventional "7+3"chemotherapy in induction young patients with acute myeloid leukemia.

This study involves the following:

Venetoclax and decitabine (investigational combination) Cytarabine and idarubicin (per standard of care)

Detailed Description

This is an open-label, multicenter, phase 2 randomized clinical trial to compare the therapeutic efficacy and safety of venetoclax and decitabine to the conventional induction chemotherapy (7+3 regimen) among fit, young adults with newly diagnosed acute myeloid leukemia (AML).

Conventional induction chemotherapy with idarubicin and cytarabine is the standard of induction chemotherapy for acute myeloid leukemia (AML).

The FDA has approved the combination therapy of venetoclax and decitabine for elderly (> 60 year old) patients with newly diagnosed AML not eligible for intensive chemotherapy. Venetoclax is an inhibitor of BCL-2 (B-cell lymphoma 2, a protein that initiates tumor growth, disease progression, and drug resistance), which can lead to cancer cell death. Decitabine, a demethylation agent, has the potential to synergically target leukemia stem cell populations when combined with venetoclax as its homologous drug azacytidine.

Participants will be randomly assigned to one of the different induction groups and followed with either consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation after remission. After completion of study treatment, participants are followed up every 3 to 6 months for up to 2 years.

It is expected that about 188 people will take part in this research study.

Conditions

AML, Adult; Chemotherapy Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Investigational ( venetoclax, decitabine)

Randomized participants will receive induction as decitabine on days 1-5 and venetoclax daily on days 1-28.

Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%):Re-induction with pre-induction therapy.

Consolidation: If patients with favorable risk and MRD (Minimal Residual Disease) negative or refuse to allo-HSCT (Hematopoietic stem-cell transplantation), intermediate-dose (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.

For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Orally by mouth

Decitabine for Injection

Intervention Type: DRUG

Intravenous infusion

Gilteritinib

Intervention Type: DRUG

Orally by mouth

Standard of Care (Conventional Induction "7+3")

Randomized participants will receive cytarabine and idarubicin per standard of care as follows:

Induction: cytarabine on days 1-7 and idarubicin (12mg/m2) on days 1-3 .

Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%): Re-induction with pre-induction therapy.

Consolidation: If patients with favorable risk and MRD negative or refuse to allo-HSCT, intermediate-dose cytarabine (2g/m2 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, intermediate-dose cytarabine for 1-2 cycles and follow up with allo-HSCT.

For patients with FLT3 mutation, gilteritinib can be combined with the follow-up treatment after the end of initial induction.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Intravenous infusion

Idarubicin

Intervention Type: DRUG

Intravenous infusion

Gilteritinib

Intervention Type: DRUG

Orally by mouth

Interventions

Venetoclax

Orally by mouth

Intervention Type: DRUG

Decitabine for Injection

Intravenous infusion

Intervention Type: DRUG

Cytarabine

Intravenous infusion

Intervention Type: DRUG

Idarubicin

Intravenous infusion

Intervention Type: DRUG

Gilteritinib

Orally by mouth

Intervention Type: DRUG

Other Intervention Names

Venclexta; Ara-C; IDA; XOSPATA

Eligibility Criteria

Inclusion Criteria

1. Male or female, 59 > =Age (years) >= 18;

2. Newly diagnosed as AML patients according to World Health Organization (WHO) 2016 classification;

3. Patients have not received prior therapy for AML (except hydroxyurea and Ara-C<1.0g/d);

4. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;

5. Liver function: Total bilirubin ≦3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN(except extramedullary infiltration of leukemia)

6. Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min;

7. Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.

Exclusion Criteria

1. Acute promyeloid leukemia；

2. AML with central nervous system (CNS) infiltration；

3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；

4. HIV infection;

5. Patients with severe heart failure (grade 3-4) ;

6. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Uncontrolled and/or active systemic infection (viral, bacterial or fungal); b) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. c) An active second cancer that requires treatment within 6 months of study entry

7. Patients deemed unsuitable for enrolment by the investigator;

8. Patients willing to receive intensive induction chemotherapy

9. Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen；

10. Patients reject to participate in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chen Suning

OTHER

Sponsor Role: lead

Responsible Party

Chen Suning

Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Suzhou, Jiangsu, China

Countries

China

References

Lu J, Xue SL, Wang Y, He XF, Hu XH, Miao M, Zhang Y, Tang ZX, Xie JD, Yang XF, Xu MZ, Shen YY, Du F, Wu Q, Xue MX, Wang Y, Deng AL, Dou XQ, Xu Y, Dai HP, Wu DP, Chen SN. Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML. Blood. 2025 May 29;145(22):2645-2655. doi: 10.1182/blood.2024027217.

Reference Type: DERIVED

PMID: 40009498 (View on PubMed)

Waclawiczek A, Leppa AM, Renders S, Stumpf K, Reyneri C, Betz B, Janssen M, Shahswar R, Donato E, Karpova D, Thiel V, Unglaub JM, Grabowski S, Gryzik S, Vierbaum L, Schlenk RF, Rollig C, Hundemer M, Pabst C, Heuser M, Raffel S, Muller-Tidow C, Sauer T, Trumpp A. Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax. Cancer Discov. 2023 Jun 2;13(6):1408-1427. doi: 10.1158/2159-8290.CD-22-0939.

Reference Type: DERIVED

PMID: 36892565 (View on PubMed)

Other Identifiers

SZ-AML02

Identifier Type: -

Identifier Source: org_study_id